title: Rational basis for the development of coenzyme Q10 as a neurotherapeutic agent for retinal protection.
abstract: Glaucoma is a worldwide leading cause of irreversible vision loss characterized by progressive death of retinal ganglion cells (RGCs). In the course of glaucoma, RGC death may be the consequence of energy impairment that triggers secondary excitotoxicity and free radical generation. There is substantial evidence also that a number of free radical scavengers and/or agents that improve mitochondrial function may be useful as therapies to ameliorate cell death in various neurological disorders including glaucoma. Coenzyme Q10 (CoQ10), an essential cofactor of the electron transport chain, has been reported to afford neuroprotection in neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, and its protective effect has been attributed in part to its free radical scavenger ability and to a specific regulation of the mitochondrial permeability transition pore. Using an established animal model of transient retinal ischemia, we have conclusively identified a role for abnormal elevation of extracellular glutamate in the mechanisms underlying RGC death that occurs, at least in part, via activation of the apoptotic program. Under these experimental conditions, N-methyl-D-aspartate (NMDA) and non-NMDA subtype of glutamate receptor antagonists, nitric oxide synthase inhibitors, and CoQ10 afford retinal protection supporting an important role for excitotoxicity in the mechanisms underlying RGC death.
authors.affiliation: Department of Pharmacobiology, University of Calabria, 87036 Arcavacata di Rende, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Russo
authors.forename: Federica
authors.initials: F
authors.lastname: Cavaliere
authors.forename: Laura
authors.initials: L
authors.lastname: Rombolà
authors.forename: Micaela
authors.initials: M
authors.lastname: Gliozzi
authors.forename: Angelica
authors.initials: A
authors.lastname: Cerulli
authors.forename: Carlo
authors.initials: C
authors.lastname: Nucci
authors.forename: Elisa
authors.initials: E
authors.lastname: Fazzi
authors.forename: Giacinto
authors.initials: G
authors.lastname: Bagetta
authors.forename: Maria Tiziana
authors.initials: MT
authors.lastname: Corasaniti
authors.forename: Luigi Antonio
authors.initials: LA
authors.lastname: Morrone
mesh_terms: D000818:Animals; D002154:Calpain / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D005901:Glaucoma / Q000188:drug therapy* / Q000473:pathology; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D018384:Oxidative Stress; D051381:Rats; D015427:Reperfusion Injury / Q000517:prevention & control; D012160:Retina / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D018696:Neuroprotective Agents; D014451:Ubiquinone; D018698:Glutamic Acid; D002154:Calpain; C024989:coenzyme Q10